DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed 01/16/2024.
Claims 40-51 are pending in the application.
Priority
This application is a DIV of 16/620,839 filed 12/09/2019 (now US Patent 11,920,159). Parent Application ’839 is a 371 of PCT/US18/36408 filed 06/07/2018.
Applicant’s claim for the benefit of a prior-filed provisional application 62/517,271 filed 06/09/2017 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Thus, the earliest possible priority for the instant application is June 09, 2017.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 40-51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are interpreted as a process of culturing mesenchymal stem cells (MSCs) with one or more vectors which encode either individually or some combination of Ostf1, Xbp1, Irf3, or Irf7 which results in revitalized mesenchymal stem cells. Furthermore, in claim 41, klf7 is additionally transduced to produce the revitalized MSC.
In the instant specification all 5 genes are required (Ostf1, Xbp1, Irf3, Irf7, klf7) in the method of making the revitalized cells (para. 0019, 0053). There is not adequate written description for a single gene transduced in an MSC which results in the claimed revitalized cell.
Moreover, there is not adequate written description that the co-culturing of transduced MSCs with HSCs (hematopoietic stem cells) or LSCs (leukemic stem cells) is part of their method of production as claimed in claims 45 and 51. Claims 45 and 51 depend on claim 40 which is a method of making the revitalized MSCs. However, it is interpreted that claims 45 and 51 are parts of a method of use, after the MSCs are produced in light of the instant specification in para. 0054 and 0046, wherein the MSCs produced are then co-cultured in a method of maintaining the other cell types.
Therefore, the claims lack adequate written description.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 45 and 47-51 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 45 and 51 are directed towards co-culture steps with HSCs and LSCs. Claims 45 and 51 depend on claim 40 which is a method of making the revitalized MSCs claimed as the invention.
However, the metes and bounds of the invention are unclear as the specification details that only the transduction of genes is required to create the revitalized MSCs. Therefore, there is no co-culture step to produce the revitalized MSCs.
It is interpreted that claims 45 and 51 are parts of a method of use, after the claimed MSCs are produced in light of the instant specification in para. 0054 and 0046, wherein the MSCs produced are then co-cultured in a method of maintaining the other cell types.
It is unclear to one of ordinary skill in the art based on the recited claims what the method of production is for the MSCs and thus renders the claims indefinite.
Claim 49 is indefinite in its recitation of “is pretreated with one or more
vector(s), the vector(s) encoding the following genes: Ostfl, Xbpl, Irf3, and Irf7”. Claim 49 depends indirectly on claim 40 where the MSCs are transduced with the same vector encoding the same one or more transgenes. Thus, it is unclear whether the MSCs are transduced twice with the same vectors , or the vectors are different but expressing the same transgenes . As such the metes and bounds of the claim are indefinite.
Claims 47-48 and 50 are indefinite insofar as they depend on claim 45 and 49, respectively.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 40, 42, 43 and 46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by West (WO2012054896A1).
The claims are interpreted as a process of culturing mesenchymal stem cells (MSCs) with one or more vectors which encode either individually or some combination of Ostf1, Xbp1, Irf3, or Irf7 which results in revitalized mesenchymal stem cells.
Regarding claim 40 and 42-43, West teaches transducing mesenchymal stem cells with one or more vectors comprising transcription factors such as Xbp1, Irf3 and Irf7 (claims 8-9, p.7 lines 21-26, p. 55 lines 34-36, p. 29 lines 7-8 & 11-15, p. 9 line 18- p. 10 line 4).
Regarding claim 46, West teaches that the MSCs are bone marrow MSCs (p. 7, lines 21-26).
Therefore, the claims are anticipated by West.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 40-43 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over West (WO2012054896A1) in view of O’ Heeron (US20160220699) and Caiazzo (“Functions of the Krüppel-like Factor 7 protein in cellular differentiation and neuronal morphogenesis”; 2009)
Claim 40 is interpreted as a process of culturing mesenchymal stem cells (MSCs) with one or more vectors which encode either individually or some combination of Ostf1, Xbp1, Irf3, or Irf7 which results in revitalized mesenchymal stem cells.
Regarding claim 40 and 42-43, West teaches transducing mesenchymal stem cells with one or more vectors comprising transcription factors such as Xbp1, Irf3 and Irf7 (claims 8-9, p.7 lines 21-26, p. 55 lines 34-36, p. 29 lines 7-8 & 11-15, p. 9 line 18- p. 10 line 4).
Regarding claim 41, West does not teach additionally delivering a vector further encoding KLF7.
O’Heeron teaches transducing mesenchymal stems cells with kIf7 in a lentiviral vector (claim 1, 4, 6, 9, 10)
Caiazzo teaches KLF7 has a suggested biological role which shows a potential direct target of stemness master genes such as Oct4 and Nanog in pluripotent stem cells like ES cells and additionally is implicated in self-renewal and stemness (p. 15, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art to transduce an MSC with kIf7 as taught by O’Heeron in addition to xpb1, irf3 and irf7 as taught by West with a reasonable expectation of success. As multiple vectors are capable of transducing into one cell, an artisan would be combining a known lentiviral vector encoding a transcription factor, KIf7, for the same purpose of transducing a cell alongside the other transcription factors in order to influence the expression of a cell. Additionally, Caiazzo teaches Klf7 is implicated in self-renewal and stemness (p. 15, 2nd paragraph).
Regarding claim 46, West teaches that the MSCs are bone marrow MSCs (p. 7, lines 21-26).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date
Claim 45 and 47-50 are rejected under 35 U.S.C. 103 as being unpatentable over West (WO2012054896A1) in view of O’ Heeron (US20160220699) and Caiazzo (“Functions of the Krüppel-like Factor 7 protein in cellular differentiation and neuronal morphogenesis”; 2009) as applied to claim 40 above and in further view of Kadekar (Stem Cell Research & Therapy (2015) 6:201).
The combination of West, O’Heeron and Caiazzo make obvious a method of transducing MSCs with Irf3, Irf7, xpb1, and klf7 under conditions sufficient to express the genes in order to increase stemness and self-renewal of the MSCs, as described above and incorporated herein in its entirety.
However, regarding claims 45, 47 and 49, West, O’Heeron and Caiazzo do not teach co-culturing with a hematopoietic stem cell (HSC) (claim 45); culturing the MSCs HSCs which are cord blood derived (claim 47) and pretreatment of MSC with one or more vectors (claim 49).
Kadekar teaches co-culture of MSCs and HSCs from cord blood and that MSCs have been proven efficient feeders for the maintenance of HSCs (Abstract, p. 3, 1st column). Ex vivo expansion of HSCs is attempted to increase the cell dose for HSC transplantation (p. 12, 2nd column). Kadekar further teaches that placental derived MSCs, cord blood derived MSCs and BM-MSCs could be co-cultured with HSCs for expansion purposes (p. 2, 1st column).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to culture the modified cells made obvious by West, O’Heeron and Caiazzo with HSCs from cord blood as taught by Kadekar with a reasonable expectation of success. An artisan would be motivated to co-culture the two cell types as Kadekar teaches MSCs have been proven efficient feeders for the maintenance of HSCs in expansion (Abstract, p. 3, 1st column) and one would be motivated to expand HSCs as it attempts to increase the cell dose for HSC transplantation (p. 12, 2nd column).
Regarding claim 48, claim 45 is made obvious by West, O’Heeron, Caiazzo and Kadekar. Moreover, Kadekar teaches that the umbilical cord blood for the HSCs and MSCs are collected from local hospitals after obtaining informed consent from individuals (p. 2, 2nd column). Therefore, it is interpreted that these cells are obtained from a subject in said hospital.
Regarding claim 50, claim 49 is made obvious by West, O’Heeron, Caiazzo and Kadekar. Moreover, as described above, Klf7 is transduced in the modified cells.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date
Claim 51 are rejected under 35 U.S.C. 103 as being unpatentable over West (WO2012054896A1) in view of O’ Heeron (US20160220699) and Caiazzo (“Functions of the Krüppel-like Factor 7 protein in cellular differentiation and neuronal morphogenesis”; 2009) as applied to claim 40 above and in further view of Ito (Stem Cell Research, 2015, 14: 95-104).
The combination of West, O’Heeron and Caiazzo make obvious a method of transducing MSCs with Irf3, Irf7, xpb1, and klf7 under conditions sufficient to express the genes in order to increase stemness and self-renewal of the MSCs, as described above and incorporated herein in its entirety.
However, regarding claim 51, West, O’Heeron and Caiazzo do not teach culturing the MSCs with leukemic stem cells (LSCs).
Ito teaches a co-culture of MSCs and LSCs in vitro (p. 96, 2nd column). Furthermore, Ito found MSCs support long-term maintenance of LSCs within the co-culture and long term maintence is important in facilitating xenotransplantaton models (p. 101, 1st column; Abstract; p. 96, 1st column).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to culture the modified cells made obvious by West, O’Heeron and Caiazzo with LSCs as taught by Ito with a reasonable expectation of success. An artisan would be motivated to co-culture the two cell types as Ito teaches MSCs support long-term maintenance of LSCs within the co-culture and long term maintence is important in facilitating xenotransplantaton models (p. 101, 1st column; Abstract; p. 96, 1st column).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date
Allowable Subject Matter
Claim 44 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
One or more vectors encoding all of Ostf1, Xbp1, Irf3, or Irf7 in order to produce the revitalized MSCs is directed towards allowable subject matter. This is detailed in the Notice of Allowance of parent application 16/620,839.
Conclusion
No claims are allowed.
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/ALEXANDRA F CONNORS/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634